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p53 mediates density‐dependent growth arrest
Author(s) -
Meerson A.,
Milyavsky M.,
Rotter V.
Publication year - 2004
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/s0014-5793(04)00027-4
Subject(s) - microbiology and biotechnology , suppressor , gene silencing , cell cycle , cell growth , embryonic stem cell , biology , cell cycle checkpoint , contact inhibition , growth inhibition , cell , genetics , cancer , gene
While the stress‐response‐associated importance of the p53 tumor suppressor is well established, recent studies have also linked p53 with several basic parameters in the normal behavior of cells. Here, we present evidence that basal p53 expression in WI38 human embryonic lung fibroblasts restricts growth rate and mediates density‐dependent inhibition of growth and the associated G1 phase arrest of the cell cycle by affecting the density‐dependent regulation of p16/INK4a. Additionally, we show that prolonged culturing of hTert‐immortalized WI38 cells leads to a loss of density‐dependent growth inhibition that correlates with p27/KIP deregulation as well as the previously shown INK4a locus silencing, and to an onset of contact‐induced, p53‐dependent cell death.